| 1. |
- Akbari, Camilla, et al.
(författare)
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Long-term major adverse liver outcomes in 1,260 patients with non-cirrhotic NAFLD
- 2024
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Ingår i: JHEP Reports. - : Elsevier. - 2589-5559. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Background & AimsLong-term studies of the prognosis of NAFLD are scarce. Here, we investigated the risk of major adverse liver outcomes (MALO) in a large cohort of patients with NAFLD.MethodsWe conducted a cohort study with data from Swedish university hospitals. Patients (n = 1,260) with NAFLD without cirrhosis were diagnosed through biopsy or radiology, and had fibrosis estimated through vibration-controlled transient elastography, biopsy, or FIB-4 score between 1974 and 2020 and followed up through 2020. Each patient was matched on age, sex, and municipality with up to 10 reference individuals from the general population (n = 12,529). MALO were ascertained from Swedish national registers. The rate of events was estimated by Cox regression.ResultsMALO occurred in 111 (8.8%, incidence rate = 5.9/1,000 person-years) patients with NAFLD and 197 (1.6%, incidence rate = 1.0/1,000 person-years) reference individuals during a median follow up of 13 years. The rate of MALO was higher in patients with NAFLD (hazard ratio = 6.6; 95% CI = 5.2–8.5). The risk of MALO was highly associated with the stage of fibrosis at diagnosis. In the biopsy subcohort (72% of total sample), there was no difference in risk between patients with and without non-alcoholic steatohepatitis. The 20-year cumulative incidences of MALO were 2% for the reference population, 3% for patients with F0, and 35% for F3. Prognostic information from biopsy was comparable to FIB-4 (C-indices around 0.73 vs. 0.72 at 10 years).ConclusionsThis study provides updated information on the natural history of NAFLD, showing a high rate of progression to cirrhosis in F3 and a similar prognostic capacity of non-invasive tests to liver biopsy.Impact and implicationsSeveral implications for clinical care and future research may be noted based on these results. First, the risk estimates for cirrhosis development are important when communicating risk to patients and deciding on clinical monitoring and treatment. Estimates can also be used in updated health-economic evaluations, and for regulatory agencies. Second, our results again highlight the low predictive information obtained from ascertaining NASHstatus by histology and call for more objective means by which to define NASH. Such methods may include artificial intelligence-supported digital pathology. We highlight that NASH is most likely the causal factor for fibrosis progression in NAFLD, but the subjective definition makes the prognostic value of a histological NASH diagnosis of limited value. Third, the finding that prognostic information from biopsy and the very simple Fibrosis-4 score were comparable is important as it may lead to fewer biopsies and further move the field towards non-invasive means by which to define fibrosis and, importantly, use non-invasive tests as outcomes in clinical trials. However, all modalities had modest discriminatory capacity and new risk stratification systems are needed in NAFLD. Repeated measures of non-invasive scores may be a potential solution.
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| 2. |
- Andreasson, Anna, et al.
(författare)
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The prediction of colorectal cancer using anthropometric measures : A Swedish population-based cohort study with 22 years of follow-up
- 2019
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Ingår i: United European Gastroenterology journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 7:9, s. 1250-1260
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is a risk factor for colorectal cancer (CRC).Objective: The objective of this article is to investigate whether anthropometric measures reflecting visceral obesity are better predictors of CRC than body mass index (BMI).Methods: Data were analysed from the Malmo Diet and Cancer study in Sweden, comprising 16,669 women and 10,805 men (median age 56.6 and 59.1 years) followed for a median 21.5 years. Diagnoses of CRC were identified using Swedish national registers. Cox regression was used to test the associations of BMI, waist circumference (WC), waist-hip ratio, waist-to-height ratio, waist-to-hip-to-height ratio, A Body Shape Index (ABSI) and percentage body fat with the development of CRC adjusted for age, alcohol consumption, smoking, education and physical activity in men and women.Results: None of the measures were significantly associated with an increased risk for CRC in women. WC was the strongest predictor of colon cancer (CC) in men and the only measure that was independent of BMI. ABSI was the only measure significantly associated with the risk of rectal cancer in men.Conclusions: Visceral obesity, best expressed as WC, is a risk factor for CC in men but a poor predictive marker for CRC in women.
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| 3. |
- Andreasson, Anna, et al.
(författare)
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Waist/Hip Ratio Better Predicts Development of Severe Liver Disease Within 20 Years Than Body Mass Index : A Population-based Cohort Study
- 2017
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Ingår i: Clinical Gastroenterology and Hepatology. - : ELSEVIER SCIENCE INC. - 1542-3565 .- 1542-7714. ; 15:8, s. 1294-1301
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Obesity, commonly assessed based on body mass index (BMI), is associated with an increased risk for severe liver disease. It is not known if other measures of body composition are better determinants of risk for severe liver disease, and/or if these differ between women and men. We investigated the body composition measures that best predict the development of severe liver disease.METHODS: We collected data from the Malmo Diet and Cancer study in Sweden, comprising 16,784 women and 10,833 (mean age, 58.1 years at baseline), and followed patients for a median 19.8 years. We analyzed data on measures of body composition including BMI, waist/hip ratio, and others. We determined whether subjects were diagnosed with severe liver disease, or died from severe liver disease, until the end of 2014 using Swedish national registers. Associations between body composition measures and severe liver disease were assessed using Cox regression models, stratified by sex and adjusted for age, alcohol consumption, smoking, education, and physical activity.RESULTS: All studied measures of body composition were significantly associated with severe liver disease. Waist/hip ratio was the best predictor of severe liver disease in women (hazard ratio [HR] per standard deviation increment, 1.30; 95% confidence interval [CI], 1.16-1.46) and men (HR, 1.46; 95% CI, 1.31-1.63). BMI had the lowest HR in women (HR, 1.12; 95% CI, 1.00-1.27) and men (HR, 1.26; 95% CI, 1.12-1.42). The association between waist/hip ratio and development of liver disease was independent of BMI.CONCLUSIONS: In a Swedish population-based cohort study, we associated all measures of body composition with risk of severe liver disease. However, measures of abdominal obesity were best at predicting development of severe liver disease.
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| 4. |
- Bengtsson, Bonnie, et al.
(författare)
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Validity of administrative codes associated with cirrhosis in Sweden
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 55:10, s. 1205-1210
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Although cirrhosisis a major cause of liver-related mortality globally, validation studies of the administrative coding for diagnoses associated with cirrhosis are scarce. We aimed to determine the validity of the International Classification of Diseases, 10th revision (ICD-10) codes corresponding to cirrhosis and its complications in the Swedish National Patient Register (NPR).Methods: We randomly selected 750 patients with ICD codes for either alcohol-related cirrhosis (K70.3), unspecified cirrhosis (K74.6) oesophageal varices (I85.0/I85.9), hepatocellular carcinoma (HCC, C22.0) or ascites (R18.9) registered in the NPR from 72 healthcare centres in 2000-2016. Hospitalisation events and outpatient visits in specialised care were included. Positive predictive values (PPVs) were calculated using the information in the patient charts as the gold standard.Results: Complete data were obtained for 630 (of 750) patients (84%). For alcohol-related cirrhosis, 126/136 cases were correctly coded, corresponding to a PPV of 93% (95% confidence interval, 95%CI: 87-96). The PPV for cirrhosis with unspecified aetiology was 91% (121/133, 95%CI: 85-95) and 96% for oesophageal varices (118/123, 95%CI: 91-99). The PPV was lower for HCC, 84% (91/109, 95%CI: 75-90). The PPV for liver-related ascites was low, 43% (56/129, 95%CI: 35-52), as this category often consisted of non-hepatic ascites. When combining the ascites code with a code for chronic liver disease, the PPV for liver-related ascites increased to 93% (50/54, 95%CI: 82-98).Conclusions: The validity of ICD-10 codes for cirrhosis, oesophageal varices and HCC is high. However, coding for ascites should be combined with a code of chronic liver disease to have an acceptable validity.
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| 5. |
- Bergman, David, et al.
(författare)
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Incidence of ICD-based diagnoses of alcohol-related disorders and diseases from swedish nationwide registers and suggestions for coding
- 2020
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Ingår i: Clinical Epidemiology. - Macclesfield, United Kingdom : Dove Medical Press Ltd.. - 1179-1349. ; 12, s. 1433-1442
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To improve consistency between register studies in Sweden and ensure valid comparisons of possible changes in alcohol-related disorders and diseases (ARDDs) over time, we propose a definition of ARDDs. Based on this definition, we examined Sweden’s incidence rates of ARDDs from 1970 to 2018 in non-primary healthcare settings (inpatient and outpatient). Methods: Swedish Society of Epidemiology members were invited to give feedback on the International Classification of Disease (ICD) codes with a potential link to alcohol use. We then calculated age-standardised and age-specific incidence of ARDDs over time according to the National Patient Register, and the lifetime prevalence of ARDDs diagnosed in adults alive in Sweden on Dec 31, 2018. Results: Sweden’s estimated incidence of ARDDs increased substantially after introducing the new ICD-9 codes in 1987. In the past 10 years (2009–2018), the incidence of ARDDs has been stable (males: 110/100,000 person-years, females: 49/100,000 person-years). Requiring at least two ICD records for diagnosed ARDDs led to a somewhat lower incidence of ARDDs (males: 71 per 100,000 person-years, females: 29 per 100,000 person-years). In Sweden, the lifetime prevalence of diagnosed ARDDs in adults on Dec 31, 2018, was 1.9% (95% CI=1.9–1.9). Conclusion: In this nationwide study, we found an incidence of ARDDs of 50–100/ 100,000 person-years. In 2018, 1 in 52 adults in Sweden had been diagnosed with ARDDs in the National Patient Register.
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| 6. |
- Ekstedt, Mattias, et al.
(författare)
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Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up
- 2015
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Ingår i: Hepatology. - : John Wiley & Sons. - 0270-9139 .- 1527-3350. ; 61:5, s. 1547-1554
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Tidskriftsartikel (refereegranskat)abstract
- Background and rationale for the study: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, strongly associated with insulin resistance and the metabolic syndrome. Nonalcoholic steatohepatitis, i.e. fatty liver accompanied by necroinflammatory changes, is mostly defined by the NAFLD activity score (NAS). The aim of the current study was to determine disease-specific mortality in NAFLD, and evaluate the NAS and fibrosis stage as prognostic markers for overall and disease-specific mortality. Methods: In a cohort study, data from 229 well-characterized patients with biopsy-proven NAFLD were collected. Mean follow-up was 26.4 (± 5.6, range 6-33) years. A reference population was obtained from the National Registry of Population, and information on time and cause of death were obtained from the Registry of Causes of Death. Main results: NAFLD patients had an increased mortality compared with the reference population (HR 1.29, CI 1.04-1.59, p=0.020), with increased risk of cardiovascular disease (HR 1.55, CI 1.11-2.15, p=0.01), hepatocellular carcinoma (HR 6.55, CI 2.14-20.03, p=0.001), infectious disease (HR 2.71, CI 1.02-7.26, p=0.046), and cirrhosis (HR 3.2, CI 1.05-9.81, p=0.041). Overall mortality was not increased in patients with NAS 5-8 and fibrosis stage 0-2 (HR 1.41, CI 0.97-2.06, p=0.07), whereas patients with fibrosis stage 3-4, irrespective of NAS, had increased mortality (HR 3.3, CI 2.27-4.76, p<0.001). Conclusions: NAFLD patients have increased risk of death, with a high risk of death from cardiovascular disease and liver-related disease. The NAS was not able to predict overall mortality, whereas fibrosis stage predicted both overall and disease-specific mortality.
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| 7. |
- Hagström, Hannes, et al.
(författare)
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Ability of Noninvasive Scoring Systems to Identify Individuals in the Population at Risk for Severe Liver Disease
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:1, s. 200-214
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Noninvasive scoring systems are used to identify persons with advanced liver fibrosis. We investigated the ability of scoring systems to identify individuals in the general population at risk for future liver-related events. METHODS: We collected data from the Swedish Apolipoprotein Mortality Risk cohort on persons 35 to 79 years old who had blood samples collected from 1985 through 1996. We collected APRI (n = 127,302), BARD (n = 75,303), FIB-4 (n = 126,941), Forns (n = 122,419), and the nonalcoholic fatty liver disease (NAFLD) fibrosis scores (NFS, n = 13,160). We ascertained incident cases of cirrhosis or complications by linking Swedish health data registers. Cox regression was used to estimate hazard ratios (HRs) for severe liver disease at 5, 10, and a maximum follow-up time of 27 years. The predictive ability of the scores was evaluated using area under the receiver operating characteristic (AUROC) curve and C-statistics analyses. Our specific aims were to investigate the predictive capabilities of scoring systems for fatal and nonfatal liver disease, determine which scoring system has the highest level of accuracy, and investigate the predictive abilities of the scoring systems in persons with a higher probability of NAFLD at baseline. RESULTS: A similar proportion of individuals evaluated by each scoring system developed cirrhosis or complications thereof (1.0%-1.4%). The incidence of any outcome was increased in intermediate- and high-risk groups compared with low-risk groups, with HRs at 10 years in the high-risk group ranging from 1.67 for the BARD score to 45.9 for the APRI score. The predictive abilities of all scoring systems decreased with time and were higher in men. All scoring systems were more accurate in persons with risk factors for NAFLD at baseline, with AUROCs reaching 0.83. CONCLUSIONS: Higher scores from noninvasive scoring systems to evaluate fibrosis are associated with an increased risk of cirrhosis in a general population, but their predictive ability is modest. Performance was better when patients were followed for shorter time periods and in persons with a higher risk of NAFLD, with AUROC values reaching 0.83. New scoring systems are needed to evaluate risk of fibrosis in the general population and in primary care.
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| 8. |
- Hagström, Hannes, et al.
(författare)
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Alcohol consumption in late adolescence is associated with an increased risk of severe liver disease later in life
- 2018
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Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 68:3, s. 505-510
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: High alcohol consumption is associated with an increased risk of severe liver disease. Current recommendations suggest it is safe for men to consume 30 grams of alcohol per day. We investigated the association between alcohol consumption early in life and later development of severe liver disease.Methods: We used data on alcohol consumption at conscription to military service from 43,296 men (18-20 years) in Sweden between 1969 and 1970. Outcomes were defined as incident diagnoses of severe liver disease from systematic national registration of clinical events until the end of 2009. A Cox regression model adjusted for body mass index, smoking, use of narcotics, cognitive ability and cardiovascular capacity was applied.Results: During a mean follow-up of 37.8 years, 383 men developed severe liver disease. Alcohol consumption was associated with an increased risk of development of severe liver disease in a dose-response pattern (adjusted hazard ratio for every one gram/day increase 1.02; 95% CI 1.01-1.02). No evidence of a threshold effect was found. Importantly, a clear trend pointed towards an increased risk of severe liver disease in men who consumed less than 30 grams of alcohol per day.Conclusion: Alcohol consumption in young men is associated with an increased risk of severe liver disease, up to 39 years later in life. The risk was dose-dependent, with no sign of a threshold effect. Current guidelines for safe alcohol intake in men might have to be revised.Lay summary: We investigated more than 43,000 Swedish men in their late teens enlisted for conscription in 1969–1970. After almost 40 years of follow-up, we found that alcohol consumption was a significant risk factor for developing severe liver disease, independent of confounders. This risk was dose-dependent, and was most pronounced in men consuming two drinks per day or more.
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| 9. |
- Hagström, Hannes, et al.
(författare)
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Body composition measurements and risk of hematological malignancies : A population-based cohort study during 20 years of follow-up
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- High body mass index (BMI) is associated with development of hematological malignancies (HMs). However, although BMI is a well-established measurement of excess weight, it does not fully reflect body composition and can sometimes misclassify individuals. This study aimed at investigating what body composition measurements had highest association with development of HM. Body composition measurements on 27,557 individuals recorded by healthcare professionals as part of the Malmo Diet and Cancer study conducted in Sweden between 1991-1996 were matched with data from national registers on cancer incidence and causes of death. Cox regression models adjusted for age and sex were used to test the association between one standard deviation increments in body composition measurements and risk of HM. During a median follow-up of 20 years, 564 persons developed an HM. Several body composition measurements were associated with risk of developing an HM, but the strongest association was found for multiple myeloma (MM). Waist circumference (HR 1.31, p = 0.04) and waist-hip ratio (HR 1.61, p = 0.05) had higher risk estimates than BMI (HR 1.18, p = 0.07) for MM. In conclusion, our study shows that measurements of abdominal adiposity better predict the risk of developing HM, particularly MM, compared to BMI.
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| 10. |
- Hagström, Hannes, et al.
(författare)
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Body mass index in early pregnancy and future risk of severe liver disease : a population-based cohort study
- 2019
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Blackwell Science Ltd.. - 0269-2813 .- 1365-2036. ; 49:6, s. 789-796
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In young men, high body mass index (BMI) has been linked to liver disease later in life, but it is unclear if this also applies to women.AIM: To study the association between BMI early in life and development of liver disease later in life in women.METHODS: We obtained data on early pregnancy BMI from 1 139 458 Swedish women between 1992 and 2015. National registers were used to ascertain incident severe liver disease, defined as cirrhosis, decompensated liver disease (hepatocellular carcinoma, oesophageal varices, hepatorenal syndrome or hepatic encephalopathy) or liver failure. A Cox regression model was used to investigate associations of BMI with incident severe liver disease adjusting for maternal age, calendar year, country of birth, smoking, civil status and education.RESULTS: (95% CI 1.02-1.05). A diagnosis of diabetes was associated with an increased risk of severe liver disease independent of baseline BMI.CONCLUSION: A high BMI early in life in women is associated with a dose-dependent, increased risk for future severe liver disease.
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